Matching Items (984)
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Description
Genomic structural variation (SV) is defined as gross alterations in the genome broadly classified as insertions/duplications, deletions inversions and translocations. DNA sequencing ushered structural variant discovery beyond laboratory detection techniques to high resolution informatics approaches. Bioinformatics tools for computational discovery of SVs however are still missing variants in the complex

Genomic structural variation (SV) is defined as gross alterations in the genome broadly classified as insertions/duplications, deletions inversions and translocations. DNA sequencing ushered structural variant discovery beyond laboratory detection techniques to high resolution informatics approaches. Bioinformatics tools for computational discovery of SVs however are still missing variants in the complex cancer genome. This study aimed to define genomic context leading to tool failure and design novel algorithm addressing this context. Methods: The study tested the widely held but unproven hypothesis that tools fail to detect variants which lie in repeat regions. Publicly available 1000-Genomes dataset with experimentally validated variants was tested with SVDetect-tool for presence of true positives (TP) SVs versus false negative (FN) SVs, expecting that FNs would be overrepresented in repeat regions. Further, the novel algorithm designed to informatically capture the biological etiology of translocations (non-allelic homologous recombination and 3&ndashD; placement of chromosomes in cells –context) was tested using simulated dataset. Translocations were created in known translocation hotspots and the novel&ndashalgorithm; tool compared with SVDetect and BreakDancer. Results: 53% of false negative (FN) deletions were within repeat structure compared to 81% true positive (TP) deletions. Similarly, 33% FN insertions versus 42% TP, 26% FN duplication versus 57% TP and 54% FN novel sequences versus 62% TP were within repeats. Repeat structure was not driving the tool's inability to detect variants and could not be used as context. The novel algorithm with a redefined context, when tested against SVDetect and BreakDancer was able to detect 10/10 simulated translocations with 30X coverage dataset and 100% allele frequency, while SVDetect captured 4/10 and BreakDancer detected 6/10. For 15X coverage dataset with 100% allele frequency, novel algorithm was able to detect all ten translocations albeit with fewer reads supporting the same. BreakDancer detected 4/10 and SVDetect detected 2/10 Conclusion: This study showed that presence of repetitive elements in general within a structural variant did not influence the tool's ability to capture it. This context-based algorithm proved better than current tools even with half the genome coverage than accepted protocol and provides an important first step for novel translocation discovery in cancer genome.
ContributorsShetty, Sheetal (Author) / Dinu, Valentin (Thesis advisor) / Bussey, Kimberly (Committee member) / Scotch, Matthew (Committee member) / Wallstrom, Garrick (Committee member) / Arizona State University (Publisher)
Created2014
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Description
The processes of a human somatic cell are very complex with various genetic mechanisms governing its fate. Such cells undergo various genetic mutations, which translate to the genetic aberrations that we see in cancer. There are more than 100 types of cancer, each having many more subtypes with aberrations being

The processes of a human somatic cell are very complex with various genetic mechanisms governing its fate. Such cells undergo various genetic mutations, which translate to the genetic aberrations that we see in cancer. There are more than 100 types of cancer, each having many more subtypes with aberrations being unique to each. In the past two decades, the widespread application of high-throughput genomic technologies, such as micro-arrays and next-generation sequencing, has led to the revelation of many such aberrations. Known types and subtypes can be readily identified using gene-expression profiling and more importantly, high-throughput genomic datasets have helped identify novel sub-types with distinct signatures. Recent studies showing usage of gene-expression profiling in clinical decision making in breast cancer patients underscore the utility of high-throughput datasets. Beyond prognosis, understanding the underlying cellular processes is essential for effective cancer treatment. Various high-throughput techniques are now available to look at a particular aspect of a genetic mechanism in cancer tissue. To look at these mechanisms individually is akin to looking at a broken watch; taking apart each of its parts, looking at them individually and finally making a list of all the faulty ones. Integrative approaches are needed to transform one-dimensional cancer signatures into multi-dimensional interaction and regulatory networks, consequently bettering our understanding of cellular processes in cancer. Here, I attempt to (i) address ways to effectively identify high quality variants when multiple assays on the same sample samples are available through two novel tools, snpSniffer and NGSPE; (ii) glean new biological insight into multiple myeloma through two novel integrative analysis approaches making use of disparate high-throughput datasets. While these methods focus on multiple myeloma datasets, the informatics approaches are applicable to all cancer datasets and will thus help advance cancer genomics.
ContributorsYellapantula, Venkata (Author) / Dinu, Valentin (Thesis advisor) / Scotch, Matthew (Committee member) / Wallstrom, Garrick (Committee member) / Keats, Jonathan (Committee member) / Arizona State University (Publisher)
Created2014
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Description
No two cancers are alike. Cancer is a dynamic and heterogeneous disease, such heterogeneity arise among patients with the same cancer type, among cancer cells within the same individual’s tumor and even among cells within the same sub-clone over time. The recent application of next-generation sequencing and precision medicine techniques

No two cancers are alike. Cancer is a dynamic and heterogeneous disease, such heterogeneity arise among patients with the same cancer type, among cancer cells within the same individual’s tumor and even among cells within the same sub-clone over time. The recent application of next-generation sequencing and precision medicine techniques is the driving force to uncover the complexity of cancer and the best clinical practice. The core concept of precision medicine is to move away from crowd-based, best-for-most treatment and take individual variability into account when optimizing the prevention and treatment strategies. Next-generation sequencing is the method to sift through the entire 3 billion letters of each patient’s DNA genetic code in a massively parallel fashion.

The deluge of next-generation sequencing data nowadays has shifted the bottleneck of cancer research from multiple “-omics” data collection to integrative analysis and data interpretation. In this dissertation, I attempt to address two distinct, but dependent, challenges. The first is to design specific computational algorithms and tools that can process and extract useful information from the raw data in an efficient, robust, and reproducible manner. The second challenge is to develop high-level computational methods and data frameworks for integrating and interpreting these data. Specifically, Chapter 2 presents a tool called Snipea (SNv Integration, Prioritization, Ensemble, and Annotation) to further identify, prioritize and annotate somatic SNVs (Single Nucleotide Variant) called from multiple variant callers. Chapter 3 describes a novel alignment-based algorithm to accurately and losslessly classify sequencing reads from xenograft models. Chapter 4 describes a direct and biologically motivated framework and associated methods for identification of putative aberrations causing survival difference in GBM patients by integrating whole-genome sequencing, exome sequencing, RNA-Sequencing, methylation array and clinical data. Lastly, chapter 5 explores longitudinal and intratumor heterogeneity studies to reveal the temporal and spatial context of tumor evolution. The long-term goal is to help patients with cancer, particularly those who are in front of us today. Genome-based analysis of the patient tumor can identify genomic alterations unique to each patient’s tumor that are candidate therapeutic targets to decrease therapy resistance and improve clinical outcome.
ContributorsPeng, Sen (Author) / Dinu, Valentin (Thesis advisor) / Scotch, Matthew (Committee member) / Wallstrom, Garrick (Committee member) / Arizona State University (Publisher)
Created2015
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Description
With the new independence of adulthood, college students are a group susceptible to adopting unsupported, if not harmful, health practices. A survey of Arizona State University undergraduate students (N=200) was conducted to evaluate supplement use, trust in information sources, and beliefs about supplement regulation. Of those who reported using supplements,

With the new independence of adulthood, college students are a group susceptible to adopting unsupported, if not harmful, health practices. A survey of Arizona State University undergraduate students (N=200) was conducted to evaluate supplement use, trust in information sources, and beliefs about supplement regulation. Of those who reported using supplements, college students most frequently received information from friends and family. STEM majors in fields unrelated to health who were taking a supplement were found to be less likely to receive information about the supplement from a medical practitioner than those in health fields or those in non-STEM majors (-26.9%, p=0.018). STEM majors in health-related fields were 15.0% more likely to treat colds and/or cold symptoms with research-supported methods identified from reliable sources, while non-health STEM and non-STEM majors were more likely to take unsupported cold treatments (p=0.010). Surveyed students, regardless of major, also stated they would trust a medical practitioner for supplement advice above other sources (88.0%), and the majority expressed a belief that dietary supplements are approved/regulated by the government (59.8%).
ContributorsPerez, Jacob Tanner (Author) / Hendrickson, Kirstin (Thesis director) / Lefler, Scott (Committee member) / College of Liberal Arts and Sciences (Contributor) / School of Molecular Sciences (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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ContributorsChandler, N. Kayla (Author) / Neisewander, Janet (Thesis director) / Sanabria, Federico (Committee member) / Olive, M. Foster (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2013-05
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Description
I propose that norms regulate behaviors that negatively impact an individual's survival and reproduction. But because monitoring and enforcing of norms can be costly, individuals should be selective about which norms they police and under what circumstances they should do so. Two studies tested this idea by experimentally activating fitness-relevant

I propose that norms regulate behaviors that negatively impact an individual's survival and reproduction. But because monitoring and enforcing of norms can be costly, individuals should be selective about which norms they police and under what circumstances they should do so. Two studies tested this idea by experimentally activating fitness-relevant motives and having participants answer questions about the policing of norms. The first study examined a norm prescribing respect for status and another proscribing sexual coercion. Results from Study 1 failed to support the hypotheses; activating a status-seeking motive did not have the predicted effects on policing of the respect-status norm nor did activating a mating motive have the predicted effects on policing of the respect-status norm or anti-coercion norm. Study 2 examined two new norms, one prescribing that people stay home when sick and the other proscribing people from having sex with another person's partners. Study 2 also manipulated whether self or others were the target of the policing. Study 2 failed to provide support; a disease avoidance motive failed to have effects on policing of the stay home when sick norm. Individuals in a relationship under a mating motive wanted less policing of others for violation of the mate poaching norm than those in a baseline condition, opposite of the predicted effects.
ContributorsSmith, M. Kristopher (Author) / Neuberg, L. Steven (Thesis director) / Presson, Clark (Committee member) / Hruschka, J. Daniel (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2013-05
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Description
Literature in public administration emphasizes a growing dissatisfaction with government on the part of residents. Where there tends to be a lack in the literature is in terms of solutions to this problem. We would like to argue that the engagement process itself has the power to foster a profound

Literature in public administration emphasizes a growing dissatisfaction with government on the part of residents. Where there tends to be a lack in the literature is in terms of solutions to this problem. We would like to argue that the engagement process itself has the power to foster a profound attitudinal shift on the part of both residents and government. This paper explores the structural and cultural barriers to satisfactory public engagement both from literature and a combination of policy analysis, semi-structured interviews and participatory observation within the City of Tempe. We then provide recommendations to the City of Tempe on how to overcome these barriers and effect authentic public engagement practices. With these new suggested practices and mindsets, we provide a way that people can have the power to create their own community.
ContributorsRiffle, Morgan (Co-author) / Tchida, Celina (Co-author) / Ingram-Waters, Mary (Thesis director) / Grzanka, Patrick (Committee member) / King, Cheryl (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2013-05
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Description
This thesis examines the relationship between unofficial, official, and parallel Islam in Uzbekistan following the end of the Soviet Union. Key touchstone moments in Uzbekistan during the twentieth-century show the history between unofficial and official Islam and the resulting precedents set for Muslims gathering against the government. This historical analysis

This thesis examines the relationship between unofficial, official, and parallel Islam in Uzbekistan following the end of the Soviet Union. Key touchstone moments in Uzbekistan during the twentieth-century show the history between unofficial and official Islam and the resulting precedents set for Muslims gathering against the government. This historical analysis shows how President Karimov and the Uzbek government view and approach Islam in the country following independence.
ContributorsTieslink, Evan (Author) / Batalden, Stephen (Thesis director) / Kefeli, Agnes (Committee member) / Saikia, Yasmin (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Politics and Global Studies (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor)
Created2013-05
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Description
Through this creative project, I executed a Distracted Driving Awareness Campaign at Arizona State University to raise awareness about the dangers of distracted driving, specifically texting while driving. As an Undergraduate Student Government Senator, my priority is the safety and success of students, both in and out of the classroom.

Through this creative project, I executed a Distracted Driving Awareness Campaign at Arizona State University to raise awareness about the dangers of distracted driving, specifically texting while driving. As an Undergraduate Student Government Senator, my priority is the safety and success of students, both in and out of the classroom. By partnering with State Farm and AT&T, we were able to raise awareness about the dangers of distracted driving and collected over 200 pledges from students to never text and drive.
ContributorsHibbs, Jordan Ashley (Author) / Miller, Clark (Thesis director) / Parmentier, Mary Jane (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Politics and Global Studies (Contributor) / Department of Psychology (Contributor) / Graduate College (Contributor)
Created2014-05
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Description
Teen dating violence is a significant problem in the U.S., with approximately 1 out of 3 teens experiencing some form of dating violence. BLOOM is a not-for-profit organization created by Donna Bartos. BLOOM's educators enter high schools in Arizona and present their educational program on dating abuse prevention. BLOOM's primary

Teen dating violence is a significant problem in the U.S., with approximately 1 out of 3 teens experiencing some form of dating violence. BLOOM is a not-for-profit organization created by Donna Bartos. BLOOM's educators enter high schools in Arizona and present their educational program on dating abuse prevention. BLOOM's primary goal is to educate teens on how to prevent teen dating violence and empower them with the skills leading to healthy relationships. After participants complete their educational program, a feedback card is filled out with an open-response section. This project focused on the open response section to analyze feedback cards through a process of code development, coding, and tallying. Information provided by this project could assist BLOOM in re-evaluating their curriculum, appealing to future investors, and growing their program to reach more students. With a coding system in place, BLOOM will also be able to better assess the impact they have on the participants of their program.
ContributorsHarmon, Ashley Nicole (Author) / Bodman, Denise (Thesis director) / Dumka, Larry (Committee member) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / College of Liberal Arts and Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05